East Kilbride and South Lanarkshire will move to tier 3 from Friday.
The move was confirmed by the First Minister on Tuesday afternoon, as she announced the region was to move out of the tier 4 restrictions.
The region has spent the past three weeks in the strictest tier of restrictions caused by the COVID-19 pandemic.
It means that shops, hairdressers, gyms and other close contact services will be allowed to reopen.
Pubs will be allowed to sell food and non-alcoholic drinks until 6pm each day.
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Shops will be allowed to open from 6am this Friday, with the other restrictions belng lifted as of 6pm at night.
First Minister Nicola Sturgeon said: ""I think today we should all allow ourselves a smile.
"This is a good day and a good moment."
The region joins the other 10 council areas in West and Central Scotland, including East Renfrewshire, in coming out of the top tier restrictions on put in place on November 20.
That was seen as a "short and sharp" effort to contain the spread of the virus, and was described as a three-week measure.
